NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype.

NSG (NOD/Scid IL2Rγnull) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn's disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor-expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.

Standards of care and determinants of women's satisfaction with delivery services in Nepal: a multi-perspective analysis using data from a health facility-based survey.

BACKGROUND: Compliance with standards of care is required for sustained improvement in the quality of delivery services. It thus represents a key challenge to improving maternal survival and meeting the Sustainable Development Goal (SDG) target of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. This study examines the extent to which normal low-risk health facility deliveries in Nepal meet the standards of quality of care and assesses the effect of the standards of quality of care and various contextual factors on women's satisfaction with the services they receive. METHODS: Drawing on the 2021 Nepal Health Facility Survey, the sample comprised 320 women who used health facilities for normal, low-risk delivery services. A weighted one-sample t-test was applied to examine the proportion of deliveries meeting the eight standards of care. Women's overall satisfaction level was computed from seven satisfaction variables measured on a Likert scale, using principal component analysis. The composite measure was then dichotomized. Binary logistic regression was used to analyze the determinants of women's satisfaction with delivery care services. RESULTS: Deliveries complying with the eight standards of care and its 53 indicators varied widely; output indicators were more frequently met than input indicators. Of the eight standards of care, the "functional referral system" performed highest (92.0%), while "competent, motivated human resources" performed the least (52.4%). Women who were attended by a provider when they called for support (AOR: 5.29; CI: 1.18, 23.64), who delivered in health facilities that displayed health statistics (AOR 3.16; CI: 1.87, 5.33), who experienced caring behaviors from providers (AOR: 2.59; CI: 1.06, 6.30) and who enjoyed audio-visual privacy (AOR 2.13; CI: 1.04, 4.38) had higher satisfaction levels compared to their counterparts. The implementation of the Maternity Incentive Scheme and presence of a maternal waiting room in health facilities, however, were associated with lower satisfaction levels. CONCLUSIONS: Nepal performed moderately well in meeting the standards of care for normal, low-risk deliveries. To meet the SDG target Nepal must accelerate progress. It needs to focus on people-centered quality improvement to routinely assess the standards of care, mobilize available resources, improve coordination among the three tiers of government, and implement high-impact programs.

Emergency obstetric and newborn care signal functions: The situation in health facilities in Nepal between 2015 and 2021.

Expanding access to facility-based delivery services and improving the functionality of emergency obstetric and neonatal care (EmONC) are important strategies toward achieving a maternal mortality ratio of 70 deaths per 100,000 live births by 2030. In this study the researchers assess signal functions at designated facilities in Nepal, using Nepal Health Facility Survey data for 2015 and 2021. The functionality of basic and comprehensive EmONC sites was low, declining over the six-year period. Lack of progress may partly be attributed to the COVID-19 pandemic. Nepal needs to expand EmONC sites strategically, strengthen referral systems, improve service readiness, and periodically assess service quality.

Changes in health facility readiness for obstetric and neonatal care services in Nepal: an analysis of cross-sectional health facility survey data in 2015 and 2021.

BACKGROUND: Nepal is committed to achieving the Sustainable Development Goal (SDG) 2030 target 3.1 of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. Along with increasing access to health facility (HF)-based delivery services, improving HF readiness is critically important. The majority of births in Nepal are normal low-risk births and most of them take place in public HFs, as does the majority of maternal deaths. This study aims to assess changes in HF readiness in Nepal between 2015 and 2021, notably, if HF readiness for providing high-quality services for normal low-risk deliveries improved; if the functionality of basic emergency obstetric and neonatal care (BEmONC) services increased; and if infection prevention and control improved. METHODS: Cross-sectional data from two nationally representative HF-based surveys in 2015 and 2021 were analyzed. This included 457 HFs in 2015 and 804 HFs in 2021, providing normal low-risk delivery services. Indices for HF readiness for normal low-risk delivery services, BEmONC service functionality, and infection prevention and control were computed. Independent sample T-test was used to measure changes over time. The results were stratified by public versus private HFs. RESULTS: Despite a statistically significant increase in the overall HF readiness index for normal low-risk delivery services, from 37.9% in 2015 to 43.7%, in 2021, HF readiness in 2021 remained inadequate. The availability of trained providers, essential medicines for mothers, and basic equipment and supplies was high, while that of essential medicines for newborns was moderate; availability of delivery care guidelines was low. BEmONC service functionality did not improve and remained below five percent facility coverage at both time points. In private HFs, readiness for good quality obstetrical care was higher than in public HFs at both time points. The infection prevention and control index improved over time; however, facility coverage in 2021 remained below ten percent. CONCLUSIONS: The slow progress and sub-optimal readiness for normal, low-risk deliveries and infection prevention and control, along with declining and low BEmONC service functionality in 2021 is reflective of poor quality of care and provides some proximate explanation for the moderately high maternal mortality and the stagnation of neonatal mortality in Nepal. To reach the SDG 2030 target of reducing maternal deaths, Nepal must hasten its efforts to strengthen supply chain systems to enhance the availability and utilization of essential medicines, equipment, and supplies, along with guidelines, to bolster the human resource capacity, and to implement mechanisms to monitor quality of care. In general, the capacity of local governments to deliver basic healthcare services needs to be increased.

Perception of Pain Expression Among Surgical Patients and Families from Three Ethnic Groups of a Nation: A Multicenter Qualitative Study.

Background: Despite its universal nature; perception, coping, responses, treatment options, and overall experiences of pain are influenced by biopsychosocial factors to various extents. Pain perception, expression, and control are progressively learned behaviors among members of a society and are culture-specific. Effects of ethnicity-related culture (ethnoculture) on pain experience in a broader context have increasingly been reported. However, evidence from ethnoculturally diverse groups of a nation, particularly based on surgical patients, is limited. Therefore, as a qualitative research effort of a broader project aimed at assessing ethnocultural determinants of surgical pain management, this study explored the perception of ethnoculturally diverse patients and families about expressing surgical disease-related pain. Methods: This study follows subjectivist-interpretivist philosophical assumptions as an underpinning research paradigm. We purposively selected 11 patients for in-depth interviews and 12 patients' family members for focus group discussions in three hospitals of ethnic-based regions of Ethiopia. In the phenomenological frame, thematic analysis was employed. Finding: Ethnocultural background influences how individuals express and respond to pain according to emergent themes of finding- Pain and overlooked cultural influence, Pain expressiveness in cultural context, Stereotypes of pain expressiveness, and Bravehood through stoic response. Pain feelings are commonly hidden where the domestic culture values stoic response to pain compared to ethnoculture where pain expressiveness is encouraged. Conclusion: Individuals can express and respond to pain differently due to ethnocultural diversity within a nation. Researchers and clinicians should consider cultural context while applying the prevailing one-size-fits-all pain assessment tools among surgical patients of a nation with ethnocultural diversity.

Cinemeducation: A mixed methods study on learning through reflective thinking, perspective taking and emotional narratives.

INTRODUCTION: Cinemeducation describes the use of film in medical education. The M23 Cinema (M23C) comprises a film screening and subsequent discussion with experts, affected persons and the audience. Previous research suggests that participating in cinemeducation may affect emotions and attitudes. This study aimed to establish a conceptual framework and explore when learning takes place, how learning occurs and what participants learn during the M23C. METHODS: Informed by focused literature searches, discussions of the authors and the research results, a conceptual framework of the M23C was developed, comprising three dimensions (five distinct phases, learning methodology and potential impact). A mixed method study was undertaken, employing an exploratory sequential design. Initially, the qualitative component was conducted by interviewing everyone involved, comprising focus groups, expert interviews, a group interview and one narrative interview. All qualitative data were analysed using qualitative content analysis. The qualitative findings were used to inform the development of a survey among the participants of M23C evenings. The survey results were analysed descriptively. The findings generated by both data sets were integrated using the "following a thread" protocol and visualised by joint displays. RESULTS: In total, 15 participants in M23C courses, six members of the current and two of the former organising committee, two experts, two affected persons and the initiator of the M23C were included in the qualitative component (n = 28). A total of 503 participants responded to the survey. The qualitative data confirmed the relevance of the five phases and participants described reflective thinking, perspective taking and emotional narratives as the three dimensions of how they learned during the M23C. Participants reported a change in attitudes, enriching their knowledge, experiencing empathy and learning about other health professions. DISCUSSION: Our findings suggest that the M23C as a cinemeducation course provides a unique learning environment in the training of health professionals.

Diagnosing virtual patients: the interplay between knowledge and diagnostic activities.

Clinical reasoning theories agree that knowledge and the diagnostic process are associated with diagnostic success. However, the exact contributions of these components of clinical reasoning to diagnostic success remain unclear. This is particularly the case when operationalizing the diagnostic process with diagnostic activities (i.e., teachable practices that generate knowledge). Therefore, we conducted a study investigating to what extent knowledge and diagnostic activities uniquely explain variance in diagnostic success with virtual patients among medical students. The sample consisted of N = 106 medical students in their third to fifth year of university studies in Germany (6-years curriculum). Participants completed professional knowledge tests before diagnosing virtual patients. Diagnostic success with the virtual patients was assessed with diagnostic accuracy as well as a comprehensive diagnostic score to answer the call for more extensive measurement of clinical reasoning outcomes. The three diagnostic activities hypothesis generation, evidence generation, and evidence evaluation were tracked. Professional knowledge predicted performance in terms of the comprehensive diagnostic score and displayed a small association with diagnostic accuracy. Diagnostic activities predicted comprehensive diagnostic score and diagnostic accuracy. Hierarchical regressions showed that the diagnostic activities made a unique contribution to diagnostic success, even when knowledge was taken into account. Our results support the argument that the diagnostic process is more than an embodiment of knowledge and explains variance in diagnostic success over and above knowledge. We discuss possible mechanisms explaining this finding.

Differences in perceptions of capability, autonomy, and expectations between residents and surgical team members in executing EPAs in Ethiopian medical education.

Background: Entrustable Professional Activities (EPAs) are units of professional practice that are defined as tasks or responsibilities that are entrusted to an unsupervised execution by a trainee. In 2021, a framework of 29 EPAs was developed for surgical residency training programs in Ethiopia, with the goal of residents being able to perform independently by the time they graduate. However, studies show that surgical residents lack confidence and are unable to execute EPAs autonomously upon graduation, and concerns have been raised about graduate competencies in EPA execution. The goal of this research is to assess how surgical team members judge/perceive residents' performance in executing these EPAs autonomously at the time of graduation and how residents rate their own capability and autonomy in executing EPAs in order to systematically introduce and implement EPAs in Ethiopian medical education. Methods: A survey was conducted in the Departments of Surgery at four residency training institutions in Ethiopia. All eligible surgical team members and final-year general surgery residents were invited to participate. Surgical team members were asked to rate the observed performance of a group of graduating surgical residents in each of the 29 EPAs, and residents were asked to rate their own capability in executing EPAs. The analysis focused on variations in performance ratings between surgical team members and residents, as well as across surgical team members. Results: A total of 125 surgical team members and 49 residents participated in this study. Residents rate their competence in performing these EPAs higher than surgical team members, mean 4.2 (SD = 0.63) vs. 3.7 (SD = 0.9). A statistically significant difference in perceptions of capability, autonomy, and expectations in executing EPAs was observed between the two groups of study (p = 0.03, CI: 0.51-0.95), as well as within surgical team members (p < 0.001). Conclusions: Differences in perceptions of capability, autonomy, and expectations between residents and surgical team members, as well as within faculty members, were seen in executing EPAs. There were concerns about graduate surgical residents' competence to execute EPAs autonomously at the time of graduation. Surgical team members perceived that a set of graduating surgical residents are not yet safe to perform these EPAs independently (without supervision) and still requires distant supervision.

Cinemeducation in medicine: a mixed methods study on students' motivations and benefits.

BACKGROUND: Cinemeducation courses are used to supplement more standard teaching formats at medical schools and tend to emphasise biopsychosocial aspects of health. The purpose of this paper is to explore why medical students attend the cinemeducation course M23 Cinema (M23C) at LMU Munich and whether a film screening with a subsequent expert and peer discussion benefits their studies and their future careers as medical doctors. METHODS: An exploratory sequential mixed methods study design was used. Qualitative research, i.e. three focus groups, four expert interviews, one group interview and one narrative interview, was conducted to inform a subsequent quantitative survey. Qualitative data was analysed using qualitative content analysis and quantitative data was analysed descriptively. The findings were integrated using the "following a thread" protocol. RESULTS: In total, 28 people were interviewed and 503 participants responded to the survey distributed at seven M23C screenings. Participants perceive the M23C as informal teaching where they learn about perspectives on certain health topics through the combination of film and discussion while spending time with peers. The reasons for and reported benefits of participation varied with educational background, participation frequency and gender. On average, participants gave 5.7 reasons for attending the M23C. The main reasons for participating were the film, the topic and the ability to discuss these afterwards as well as to spend an evening with peers. Attending the M23C was reported to support the students' memory with regards to certain topics addressed in the M23C when the issues resurface at a later stage, such as during university courses, in the hospital, or in their private life. CONCLUSIONS: The M23C is characterised by its unique combination of film and discussion that encourages participants to reflect upon their opinions, perspectives and experiences. Participating in the M23C amplified the understanding of biopsychosocial aspects of health and illness in students. Thus, cinemeducative approaches such as the M23C may contribute to enabling health professionals to develop and apply humane, empathetic and relational skills.

Development of an Entrustable Professional Activities (EPA) Framework to Inform Surgical Residency Training Programs in Ethiopia: A Three-round National Delphi Method Study.

BACKGROUND: Entrustable Professional Activities (EPAs) have been proposed as a means to translate competencies into clinical practice. Although EPAs for residency training have become available, 1 set of core EPAs cannot automatically be transferred from one context to another due to cultural variability. Further, there is a lack of African- and Asian-based EPA development and implementation studies. We developed an end-of-training EPAs framework to inform surgical residency training programs in the local context of Ethiopian medical education. METHODS: A three-round Delphi method was used to establish consensus about important surgical EPAs among experts. A total of 136 experts representing all surgical residency training institutions in Ethiopia were invited to participate. Round 1 & 2 consisted of senior expert panelists (n = 8) to identify potential EPAs and determine the content validity. Round 3 consisted of a survey (n = 128) to further validate the identified EPAs by attending surgeons who work with them. Each EPA had to achieve at least 80% or higher agreement among experts to be considered having acceptable content validity. RESULTS: In round 1, a total of 272 EPAs were proposed, reduced, and grouped to 39 consented EPAs. In round 2, the same experts rated each EPA's relevance, resulting in 32 EPAs with a satisfactory item-level content validity index (I-CVI > 0.83). Overall, in the survey in round 3, 29 EPAs met the standard criterion for acceptability (S-CVI/Ave = 0.90) and achieved a high degree of final consensus (ICC = 0.998, 95% CI [0.996, 0.999]; (F = 439.2, p < 0.0001). CONCLUSIONS: The framework of 29 validated and accepted EPAs can guide future surgical residency training programs in the Ethiopian medical education context. The framework allows programs to move from a time-dependent to an outcome-based model and transforms traditional assessment into entrustment decisions. Thus, the use of the framework can improve the quality of training and patient care in Ehtiopia.

Evidence Gaps and Challenges in the Fight Against COVID-19 in Africa: Scoping Review of the Ethiopian Experience.

BACKGROUND: Ethiopia, like many African countries, took immediate actions to contain the coronavirus disease (COVID-19) outbreak and its impacts. However, the pandemic control measures were not guided by robust local evidence and not tailored to national contexts. In this review, we aimed to evaluate the evidence gaps and challenges of COVID-19 control measures in Ethiopia during the early months of the pandemic. DESIGN: Scoping Review. DATA SOURCE: Searches were conducted in PubMed, LitCovid, Web of Sciences, Embase, MedRx, ChemRxiv, BioRx, and Google Scholar. ELIGIBILITY CRITERIA: Peer-reviewed or pre-print original research articles on COVID-19 from Ethiopia during a period of January 1, 2020 and October 10, 2020 were included in this review. RESULTS: Of 573 articles found, 64 were eligible for inclusion. However, only 25 of them were peer-reviewed; 78% (50/64) were based on cross-sectional descriptive studies. Most of the studies focused on human behavior and healthcare system; only 13 articles addressed epidemiology and clinical spectrum of COVID-19. The studies have revealed a good level of awareness and a favorable attitude by community and healthcare workers (HCWs) towards COVID-19 and its control. However, the practices of infection prevention were found to be low among HCWs and the community. The outbreak unfolded at a slower rate than initially feared but the impact of the counter measures against COVID-19 on the delivery of essential healthcare services was felt more than the direct impact of the pandemic. Moreover, the actions taken by the country did not appear to be tailored to the pattern of the outbreak and existing local evidence. The overall number of published COVID-19-related scientific articles from Ethiopia during the review period was found to be limited. CONCLUSION: COVID-19 control in Ethiopia was challenged by lack of robust local scientific evidence, and the pandemic control measures were not adapted to local context and the outbreak patterns. Thus, Ethiopia and other African countries should design culturally sensitive and locally acceptable public health interventions for COVID-19 and potential future outbreaks based on locally generated scientific evidence.

Learning to diagnose accurately through virtual patients: do reflection phases have an added benefit?

BACKGROUND: Simulation-based learning with virtual patients is a highly effective method that could potentially be further enhanced by including reflection phases. The effectiveness of reflection phases for learning to diagnose has mainly been demonstrated for problem-centered instruction with text-based cases, not for simulation-based learning. To close this research gap, we conducted a study on learning history-taking using virtual patients. In this study, we examined the added benefit of including reflection phases on learning to diagnose accurately, the associations between knowledge and learning, and the diagnostic process. METHODS: A sample of N = 121 medical students completed a three-group experiment with a control group and pre- and posttests. The pretest consisted of a conceptual and strategic knowledge test and virtual patients to be diagnosed. In the learning phase, two intervention groups worked with virtual patients and completed different types of reflection phases, while the control group learned with virtual patients but without reflection phases. The posttest again involved virtual patients. For all virtual patients, diagnostic accuracy was assessed as the primary outcome. Current hypotheses were tracked during reflection phases and in simulation-based learning to measure diagnostic process. RESULTS: Regarding the added benefit of reflection phases, an ANCOVA controlling for pretest performance found no difference in diagnostic accuracy at posttest between the three conditions, F(2, 114) = 0.93, p = .398. Concerning knowledge and learning, both pretest conceptual knowledge and strategic knowledge were not associated with learning to diagnose accurately through reflection phases. Learners' diagnostic process improved during simulation-based learning and the reflection phases. CONCLUSIONS: Reflection phases did not have an added benefit for learning to diagnose accurately in virtual patients. This finding indicates that reflection phases may not be as effective in simulation-based learning as in problem-centered instruction with text-based cases and can be explained with two contextual differences. First, information processing in simulation-based learning uses the verbal channel and the visual channel, while text-based learning only draws on the verbal channel. Second, in simulation-based learning, serial cue cases are used to gather information step-wise, whereas, in text-based learning, whole cases are used that present all data at once.

NOD/scid IL-2Rγnull mice reconstituted with peripheral blood mononuclear cells from patients with Crohn's disease reflect the human pathological phenotype.

INTRODUCTION: Crohn's disease (CD) is characterized by pronounced intestinal fibrosis and severe mucosal damage and conventional animal models are limited to reflect these pathological manifestations. The aim of this study was to examine whether the combination of patient immune-profiling and preclinical studies in a mouse model based on NOD/scid IL-2Rγnull (NSG) reconstituted with peripheral blood mononuclear cells (PBMC) from CD patients has the capacity to harmonize ex vivo human and in vivo animal studies. METHODS: Immunological profiles of CD (n = 24) and ulcerative colitis (UC) patients (n = 47) were established by flow cytometry of subgroups of immune cells and subjected to hierarchical cluster and estimation graphics analyses. Pathological phenotypes of NSG mice, which were reconstituted with PBMC from CD, UC, and non-IBD donors (NSG-CD, NSG-UC, and NSG-non-IBD) were compared. Readouts were the clinical, colon, and histological scores; subtypes of immune cells from spleen and colon; and levels of inflammatory markers, such as c-reactive protein (CRP), monocyte chemotactic protein (MCP)-3, transforming growth factor-beta (TGFß), and hepatocyte growth factor (HGF). Fibrocytes were identified by immunohistochemistry in colonic sections. RESULTS: CD patients were significantly clustered in a group characterized by increased levels of TH1, TH2 cells, and decreased levels of CD14+ CD163+ monocytes (p = .003). In contrast to NSG-UC mice, NSG-CD mice exhibited an immune-remodeling phenotype characterized by enhanced collagen deposition, elevated levels of CD14+ CD163+ monocytes, HGF, and TGFß. This phenotype was further corroborated by the presence of human fibrocytes as components of fibrotic areas. CONCLUSION: The NSG-CD model partially reflects the human disease and allows for studying the development of fibrosis.

Neonatal Hyperbilirubinemia treatment by Locally Made Low-Cost Phototherapy Units.

BACKGROUND: Hyperbilirubinemia is a very common finding in neonates and may occasionally cause severe morbidity and even mortality. Severe hyperbilirubinemia is typically treated, either with phototherapy or exchange transfusions. This study assessed the effectiveness of a locally manufactured phototherapy device for reducing serum bilirubin in neonates with severe hyperbilirubinemia. METHODS: Retrospective chart review was carried out to assess the outcome of 32 infants who were treated for neonatal hyperbilirubinemia at Jimma Medical Center (JMC) from May, 2017 to April, 2018. RESULTS: Out of 75 charts reviewed, only 32 had subsequent bilirubin level determination, 18(56.3%) of them were males. The age at which jaundice was noticed and confirmed with plasma bilirubin level was 4 ± 2.7 days (mean±SD). Sepsis was thought to be the cause of hyperbilirubinemia in 13(40.5%) of the cases, while hemolysis from ABO incompatibility or RH incompatibility contributed in 5(15.6%) and 3(9.4) of the infants respectively. The mean (minimum, maximum) level of baseline TSB was 21.4(14, 55) mg/dL. Five infants (15.6%) had exchange transfusions because of extreme hyperbilirubinemia. The duration of phototherapy and decline in TSB were 5.34 ±2.8 days and 2.2±1.5mg/dl/day (mean±SD) respectively. The levels of TSB before and at the end of phototherapy were significantly different (p<0.001). CONCLUSION: Acceptable reduction of TSB was achieved by using locally manufactured PT devices. Benefits included better accessibility and lower price and maintenance costs. High mean baseline TSB was observed, and duration of phototherapy is prolonged which could indicate late diagnosis compared to similar studies.

The PI3K pathway as a therapeutic intervention point in inflammatory bowel disease.

With glucose being the preferred source of energy in activated T cells, targeting glycolysis has become an attractive therapeutic intervention point for chronic inflammatory bowel diseases (IBD). The switch to glycolysis is mediated by phosphoinositide-3-kinases (PI3K) which relay signals from surface receptors to the AKT pathway. We first confirmed by analysis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) that metabolism is shifted towards glycolysis in IBD patients as compared to non-IBD donors. In contrast to non-IBD donors, OCR correlated with ECAR (IBD: cor = 0.79, p = 2E-10; non-IBD: cor = 0.37, p = n.s.), in IBD patients. Second, we tested the PI3K inhibitor copanlisib as a potential therapeutic. Ex vivo, copanlisib suppressed the ECAR significantly in T cells activated by anti-CD3 antibodies and significantly decreased ECAR rates in the presence of copanlisib (anti-CD3: 58.24 ± 29.06; copanlisib: 43.16 ± 20.23, p < .000. In addition, copanlisib impaired the activation of CD4+ CD25+ T cells (anti-CD3: 42.15 ± 21.46; anti-CD3 + copanlisib: 26.06 ± 21.82 p = .013) and the secretion of cytokines (IFNγ: anti-CD3: 6332.0 ± 5707.61 pmol/ml; anti-CD3 + copanlisib: 6332.0 ± 5707.61, p = .018). In vivo, copanlisib significantly improved the histological scores (ethanol: 8.5 ± 3.81; copanlisib: 4.57 ± 2.82, p = .006) in the NSG-UC mouse model. Orthogonal partial least square analysis confirmed the efficacy of copanlisib. These data suggest that the PI3K pathway provides an attractive therapeutic intervention point in IBD for patients in relapse. Targeting metabolic pathways have the potential to develop phase dependent therapies.

Establishment of a Pediatric Surgical Unit at a University Hospital in Eastern Africa.

INTRODUCTION: Ethiopia is a rapidly developing country in Eastern Africa. In total, 43.2% of the population are younger than 15. In contrast, until a few years ago, pediatric surgery was only available in Addis Ababa. Now, Ethiopia is making great efforts to improve the care of children who require surgery. JimmaChild was established to set up a pediatric surgery in Jimma. MATERIAL AND METHODS: JimmaChild developed from a scientific collaboration between Jimma University (JU) and Ludwig-Maximilians-University. The project was developed and realized by Ethiopian and German colleagues. A curriculum was written for this purpose. The pediatric surgical training of the fellows was carried out on-site by German pediatric surgeons. RESULTS: A new pediatric surgery was established at JU with its own operating room, ward, and staff. After two and a half years, two fellows completed their final examinations as pediatric surgeons. Among others, 850 elective surgeries were performed, 82% assisted by the German colleagues. The German colleagues rated the preparation for the trip, the on-site support, and the professional progress of the fellows mostly as good to very good. Reported problems in the program flow were also recognized and solved in part. CONCLUSIONS: The best possible integration of the project into existing structures was achieved by close cooperation of Ethiopian and German colleagues during the project development. Problems were identified and addressed early on by external monitoring. As the project responsibility was mainly with the Ethiopian colleagues, a department was created that now exists independently of external funding and trains its own fellows.

Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis.

BACKGROUND AND AIMS: The potassium channel Kv1.3 is a potentially attractive therapeutic target in T cell-mediated inflammatory diseases, as the activity of antigen-activated T cells is selectively impeded by Kv1.3 inhibition. In this study, we examined Kv1.3 as a potential therapeutic intervention point for ulcerative colitis [UC], and studied the efficacy of DES1, a small-molecule inhibitor of Kv1.3, in vitro and in vivo. METHODS: Kv1.3 expression on T cells in peripheral blood mononuclear cells [PBMCs] isolated from donors with and without UC was examined by flow cytometry. In biopsies from UC patients, Kv1.3-expressing CD4+ T cells were detected by flow cytometry and immunohistochemistry. In vitro, we determined the ability of DES1 to inhibit anti-CD3-driven activation of T cells. In vivo, the efficacy of DES1 was determined in a humanised mouse model of UC and compared with infliximab and tofacitinib in head-to-head studies. RESULTS: Kv1.3 expression was elevated in PBMCs from UC patients and correlated with the prevalence of TH1 and TH2 T cells. Kv1.3 expression was also detected on T cells from biopsies of UC patients. In vitro, DES1 suppressed anti-CD3-driven activation of T cells in a concentration-dependent manner. In vivo, DES1 significantly ameliorated inflammation in the UC model and most effectively so when PBMCs from donors with higher levels of activated T cells were selected for reconstitution. The efficacy of DES1 was comparable to that of either infliximab or tofacitinib. CONCLUSION: Inhibition of Kv1.3 [by DES1, for instance] appears to be a potential therapeutic intervention strategy for UC patients.

Assessment of Diagnostic Competences With Standardized Patients Versus Virtual Patients: Experimental Study in the Context of History Taking.

BACKGROUND: Standardized patients (SPs) have been one of the popular assessment methods in clinical teaching for decades, although they are resource intensive. Nowadays, simulated virtual patients (VPs) are increasingly used because they are permanently available and fully scalable to a large audience. However, empirical studies comparing the differential effects of these assessment methods are lacking. Similarly, the relationships between key variables associated with diagnostic competences (ie, diagnostic accuracy and evidence generation) in these assessment methods still require further research. OBJECTIVE: The aim of this study is to compare perceived authenticity, cognitive load, and diagnostic competences in performance-based assessment using SPs and VPs. This study also aims to examine the relationships of perceived authenticity, cognitive load, and quality of evidence generation with diagnostic accuracy. METHODS: We conducted an experimental study with 86 medical students (mean 26.03 years, SD 4.71) focusing on history taking in dyspnea cases. Participants solved three cases with SPs and three cases with VPs in this repeated measures study. After each case, students provided a diagnosis and rated perceived authenticity and cognitive load. The provided diagnosis was scored in terms of diagnostic accuracy; the questions asked by the medical students were rated with respect to their quality of evidence generation. In addition to regular null hypothesis testing, this study used equivalence testing to investigate the absence of meaningful effects. RESULTS: Perceived authenticity (1-tailed t81=11.12; P<.001) was higher for SPs than for VPs. The correlation between diagnostic accuracy and perceived authenticity was very small (r=0.05) and neither equivalent (P=.09) nor statistically significant (P=.32). Cognitive load was equivalent in both assessment methods (t82=2.81; P=.003). Intrinsic cognitive load (1-tailed r=-0.30; P=.003) and extraneous load (1-tailed r=-0.29; P=.003) correlated negatively with the combined score for diagnostic accuracy. The quality of evidence generation was positively related to diagnostic accuracy for VPs (1-tailed r=0.38; P<.001); this finding did not hold for SPs (1-tailed r=0.05; P=.32). Comparing both assessment methods with each other, diagnostic accuracy was higher for SPs than for VPs (2-tailed t85=2.49; P=.01). CONCLUSIONS: The results on perceived authenticity demonstrate that learners experience SPs as more authentic than VPs. As higher amounts of intrinsic and extraneous cognitive loads are detrimental to performance, both types of cognitive load must be monitored and manipulated systematically in the assessment. Diagnostic accuracy was higher for SPs than for VPs, which could potentially negatively affect students' grades with VPs. We identify and discuss possible reasons for this performance difference between both assessment methods.

Head-to-head study of oxelumab and adalimumab in a mouse model of ulcerative colitis based on NOD/Scid IL2Rγnull mice reconstituted with human peripheral blood mononuclear cells.

This study's aim was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) might lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134; also known as TNFRSF4) and CD14+ monocytes expressing OX40L (CD252; also known as TNFSF4) by flow cytometric analysis. A significant difference was observed between the groups for CD14+ OX40L+ (UC: n=11, 85.44±21.17, mean±s.d.; non-UC: n=5, 30.7±34.92; P=0.02), whereas no significant difference was detected for CD4+ OX40+. CD14+ OX40L+ monocytes were correlated significantly with T helper 1 and 2 cells. Second, NOD/Scid IL2Rγ null mice were reconstituted with peripheral blood mononuclear cells from UC donors exhibiting elevated levels of OX40L, and the efficacy of oxelumab was compared with that of adalimumab. The clinical, colon and histological scores and the serum concentrations of IL-6, IL-1ß and glutamic acid were assessed. Treatment with oxelumab or adalimumab resulted in significantly reduced clinical, colon and histological scores, reduced serum concentrations of IL-6 and reduced frequencies of splenic human effector memory T cells and switched B cells. Comparison of the efficacy of adalimumab and oxelumab by orthogonal partial least squares discrimination analysis revealed that oxelumab was slightly superior to adalimumab; however, elevated serum concentrations of glutamic acid suggested ongoing inflammation. These results suggest that oxelumab addresses the pro-inflammatory arm of inflammation while promoting the remodeling arm and that patients exhibiting elevated levels of OX40L might benefit from treatment with oxelumab.

Disparity in Birth Size of Ethiopian Preterm Infants in Comparison to International INTERGROWTH-21st Data.

Background. Patterns of fetal growth are largely influenced by environmental, nutritional, and socioeconomic factors more than differences in populations. The aim of this study was to assess anthropometric measurements of Ethiopian preterm infants at birth and compare the results with the international INTERGROWTH-21st data. Patients and methods. We analyzed anthropometric data on live-born singleton preterm infants enrolled in a hospital-based multicenter study of illness in preterm infants (SIP). Eligible newborns with gestational age of 28-36 weeks were included. Gestational age (GA) and sex-specific mean and standard deviations (SD), 10th, 50th, 90th, centile values for birth weight, length and head circumference (HC) were calculated and compared with INTERGROWTH-21st data. Result. A total of 2763 preterm infants were included in the study, 54% were male. The prevalence of small for GA (SGA) (<10th percentile) and large for GA (LGA) (>90th percentile) were 10.8% and 9.9%, respectively. In all 3 parameters, the mean values of boys were higher than of girls. Birth weight centiles were comparable to international averages at lower GA, then after GA of 32 weeks the 10th, 50th, and 90th centile values were 100-500 g less than the international averages. The head circumference centiles were mostly comparable, and the 90th centile values were greater than the international averages across the GA and in both sexes. Conclusion. The infants' birth weights were smaller at higher GA, which may indicate maternal undernutrition in the third trimester of pregnancy. Strengthening antenatal nutrition counseling and providing nutrition supplementation might improve the birth weight.